This proposal outlines the development of molecular biology techniques to clone monoclonal antibodies (MAbs). Murine MAbs are being used in many clinical applications such as cancer, septic shock and transplantation. the use of human MAbs would obviate the human anti-mouse MAb response which often blunts the clinical usefulness of MAb immunotherapy. However, for most indications human MAbs are very difficult or impossible to obtain. Human MAbs made by the proposed method may not have the same restrictions as conventionally produced MAbs and thus could be of great practical utility. The recombinant DNA cloning techniques that we have designed will allow us to replicate a human antibody response to either a foreign antigen, such as AIDS virus coat protein, or self antigens, such as tumor markers. A successful replica cloning strategy will greatly facilitate the identification of clinically useful human monoclonal antibodies.